Synthesis and Antiviral Activity of Novel Phosphorylated Derivatives of Didanosine Against Newcastle Disease Virus in Chicken

Abstract

A series of novel phosphorylated derivatives of didanosine were designed and docking studies were performed with a fusion protein of the Newcastle disease virus (NDV), to develop antiviral compounds against NDV. Based on the docking scores and binding affinities, three derivatives were selected. These compounds were synthesized and characterized by IR, (1) H, (13) C, (31) P, and CHN analysis and mass spectra. They were assessed for their in vitro antiviral activity in DF-1 cells; DDI-10 showed better antiviral activity as evidenced by significant reduction in plaque formation and cytopathic effects. DDI-10 was further evaluated in NDV-infected chicken; the survival rates and antioxidant enzyme levels in brain, liver, and lung tissues were estimated. Superoxide dismutase and catalase were significantly raised, and lipid peroxidation and HA titer levels were decreased upon treatment with 1.5 mg/kg body weight of DDI-10 than with 3 mg/kg body weight of DDI. Further histopathological alterations in NDV-infected tissues were restored in chicken treated with DDI-10. Thus, based on the results from in silico, in vitro, and in vivo assays, the novel phosphorylated DDI-10 might be considered as potent antiviral compound for NDV infection in chicken.

Antiviral Chemotherapy in Avian Medicine—A Review

“…Phosphorylated didanosine derivates are designed [ 29 , 31 , 83 ] to overcome the disadvantages of didanosine, such as a short plasma half-life, low bioavailability, and dose-dependent cellular toxicities; it is unstable in its acidic conditions [ 84 ] and has poor permeability through intestinal epithelium and low oral bioavailability [ 85 ]. In one study, phosphorylated didanosine derivate DDI-10 was chosen from a series of designed derivates and showed antiviral activity against NDV in vitro, as evidenced by a significant reduction in plaque formation and cytopathic effects [ 86 ].…”

“…In vivo, in NDV-infected chicken, it was shown that superoxide dismutase and catalase were significantly raised, and lipid peroxidation and HA titer levels were decreased upon treatment with 1.5 mg/kg BW of DDI-10 compared to 3 mg/kg BW of DDI [ 86 ]. Histopathological alterations in NDV-infected tissues were restored in chickens treated with DDI-10.…”

Synthesis, Spectral Characterization, Docking Studies and Antiviral Activity of Phosphorylated Derivatives of Lopinavir Intermediate

“…Previously several researchers proved the NDV inhibitory activity of aminated nucleosides . It was found that amino acid esters are used as pro‐drugs of nucleoside namely Valacyclovir, L ‐valine can easily diffuse across the intestine mediated by the intestinal proton‐coupled peptide transporter which resulted in increase of oral absorption, such as Acyclovir and Ganciclovir …”